Candidate: Dr. Elizabeth Yoder has a strong background in mouse brain imaging using optical techniques, and has received recent training in functional magnetic resonance imaging (fMRI) in humans. Her long-term career goal is to become an independent investigator who studies the principles and mechanisms of neurovascular coupling using mouse models. Her immediate objective is to pursue a rigorous period of developing the fMRI technology to enable this goal. She has designed a career development plan that incorporates this development of new technology to use fMRI for measurement of cerebral blood flow, cerebral blood oxygenation, and cerebral oxygen metabolism in mice. Environment: The rich research environment at the University of California, San Diego and its affiliated institutions is ideal for the candidate's career development. Dr. Yoder will be mentored by Dr. Buxton, Director of the new UCSD Center for fMRI, a facility dedicated to fMRI research in humans and animals. Part of the Center's core research program uses fMRI to study neurovascular coupling, and Dr. Yoder's participation in this program will provide her with valuable contacts and collaborations. The Center has the necessary resources for Dr. Yoder to accomplish her goals. Research: The mouse is the species of choice for generating animal models of disease and disability. Coordinated international efforts to sequence the mouse genome were just successfully completed. Accordingly, the research emphasis must now shift to generating genetically-modified animals and characterizing their phenotypes. Existing schemes for phenotyping mice utilize anatomical and behavioral strategies. This application proposes to develop a physiological phenotyping protocol using functional magnetic resonance imaging (fMRI). Specifically, technology will be developed that simultaneously and dynamically measures both cerebral blood flow and cerebral blood oxygenation. This capability will be crucial to the evaluation of mouse models of numerous neurological diseases that have vascular deficits, such as Alzheimers Disease, Parkinson's Disease, and stroke. Once developed, the proposed technology will not only be useful for characterization of mouse phenotypes, it will provide a useful, quantitative physiological metric for comparing the efficacy of treatment regimes in these mouse models, and it will enhance the usefulness of mouse models for investigation of basic biological processes. The proposed technology is not envisaged as a primary screen for "baseline" phenotyping but rather as a secondary screening for deficits in cerebral blood flow and energy metabolism. The endpoint of the project will be the submission of a novel phenotyping protocol to the Mouse Phenome Database.